Formaldehyde (HCHO) is a ubiquitous air pollutant, and the prolonged inhalation poses a serious threat to human health, thus it is imperative to develop HCHO oxidation catalysts with high activity. FeNx-based catalysts have shown brilliant catalytic performance due to their unique electronic structures. In this work, the active FeN3 site is designed by doping Fe atom at the B-vacancy in BN monolayer without introducing additional N atoms. Our first principles calculation results show that the Fe atom has good dispersibility, dynamical stability and thermal stability on the BN monolayer. Two oxidation mechanisms (Langmuir-Hinshelwood and Eley-Rideal) of HCHO on Fe-doped BN monolayer are investigated to explore the possible reaction pathways. The dissociation of O2 molecule is identified as the rate-limiting step, and the lowest energy barrier is 0.99 eV. Moreover, the excellent desorption behaviors of the produced CO2 and H2O molecules on substrate (small desorption energy of 0.20 and 0.75 eV, and short desorption time of 2.39 × 10−9 and 4.64 s) enable this catalyst to maintain high activity during the reaction cycle. Our results suggest the feasibility of Fe-doped BN monolayer for the catalytic oxidation of HCHO and broaden the application of BN-based single-atom catalysts.